Synthesis of [ 11C]tetrabenazine, a vesicular monoamine uptake inhibitor, for PET imaging studies

Abstract

Tetrabenazine (TBZ), a high affinity and specific inhibitor of the vesicular monoamine transporter, has been labeled with carbon-11 as a potential probe for in vivo positron emission tomographic imaging of monoaminergic neuronal losses in neurodegenerative diseases. [ 11C]TBZ was synthesized by O-[ 11C]methylation of the 9- O-desmethylTBZ using [ 11C]methyl iodide in the presence of tetrabutyl-ammonium hydroxide. The radiochemical yields were 35–55% (decay corrected) and the synthesis time 32–37 min from EOB. [ 11C]TBZ was obtained with specific activities of 2000–2500 Ci/mmol (EOS) and radiochemical and chemical purities were >95%. [ 11C]Tetrabenazine is a promising new radioligand for the in vivo study of monoaminergic neurons using PET.